This postdoctoral training program proposal is designed to train fellows, principally surgeons, for a period of two-to-three years each, in basic science research relevant to trauma and sepsis. Funds to support a total of five positions each year (two new fellows each year, two second year positions, and one third-year) are requested. The overall research focus of the trainees is the molecular biology of the inflammatory response to injury. Three areas of research have been targeted: I) The molecular biology of hemorrhagic and traumatic shock; II) The regulation and function of nitric oxide in sepsis and trauma; and III) Mechanisms of immunoregulation in surgical patients. These areas coincide with current extramural research grants on which the faculty collaborate. The research plans are superb vehicles for training because they ask broad questions on which precise, well-targeted individual research training efforts can be staged. The faculty is highly qualified, and all principle trainers have extramural research support and much training experience. Upon completion of the training program the fellow will understand how to design, carry out, and complete experiments to answer discrete biological questions derived from trauma victims and septic patients. The fellow will thus be trained, not simply in the sophisticated laboratory methodology in molecular biology, biochemistry, and cellular immunology, but also in the though processes to apply to future experimental problems. All trainees will have the opportunity to take formal academic courses offered by the basic science departments of the University of Pittsburgh and some will complete PhDs in the basic science departments. Most training will take place in the laboratories of the principle trainers who are all extramural grant-funded senior scientists in the areas of molecular biology, biochemistry, immunology, and cell biology, using a carefully though-out and well-proven modification of the master/apprentice system. The central training technique combines weekly one-on-one meetings between the apprentice and the trainer plus hour- long research training seminars twice weekly at which supervision subcommittees of four or five trainers, whose special skills supplement the friendly collaborative research and training simultaneously. The individual fellows choose a principle trainer and the Executive Training Committee tailors a fellowship supervising committee of faculty co- trainers to provide expert training necessary to supplement the talents of the principal trainer. Affirmative action recruitment efforts have already been very successful, and will continue; the training facilities can serve more fellows than will be funded by this training proposal. All the training can be carried out in the more than 50,000 square feet of fully equipped laboratory space available.